Summary The URGENT Native American ECHO Cohort will build on the active Navajo Birth Cohort Study (NBCS), extending the follow up period beyond the current 12 month protocol, and adding two additional tribes, the Cheyenne River and Oglala Sioux Tribes, to assess the impact of environmental exposures to abandoned mine waste on birth outcomes and child development. The study, the first large-scale assessment of environmental exposures and children?s health in tribal populations is conducted in partnership with tribal communities and will help to build both research capacity within the tribes as well as capacity of tribal staff to conduct detailed developmental assessments. The study will follow development of the enrolled children until age 5 to track trajectories or patterns of neuro- and physical development with respect to environmental exposures to metal mixtures from abandoned hard rock and uranium mines on or near tribal lands. There are 161,000 such abandoned mines in the Western US, 4,000 of them abandoned uranium mines which are often unfenced, unmarked and accessible to children. On Navajo Nation alone, more than 500 abandoned uranium mines remain un-remediated more than 30 years since the closing of the last mine. The proposed research will address two of the key health outcome focus areas identified by the ECHO program through study of the effects of prenatal and early childhood exposure on 1) neurodevelopment, and 2) obesity. Based on the team?s preliminary findings, the research will focus on dysregulation of immune function as a result of exposure to metal mixtures during gestation, and mechanisms by which this dysregulation can lead to neurodevelopmental delays and obesity. The work will be conducted as part of the NIH Consortium to study Environmental Influences on Child Health Outcomes (ECHO) which will attempt to bring together as many as 50,000 children from existing birth cohort studies to understand the complex interactions of toxicant, social, nutritional, and cultural environments on developmental trajectories. Inclusion of the Native American Cohort will bring to the Consortium the first in-depth look at how normal child development progresses in Native populations in addition to how environmental adversity affects that course. Native Americans have far greater rates of poverty and unemployment, lack much essential infrastructure including clean drinking water and sewers, and have lower educational completion rates. However, they also have strong cultural identities, strength in child- rearing from extended families, and differences in appreciation of significant developmental milestones that have been associated with the development of resilience that helps in overcoming adversity. Therefore, their inclusion in this effort to understand the effects of exposure on these important health outcomes will bring a perspective that will serve not only to inform our understanding of development in the US through inclusion of the diversity represented by the sovereign tribal nations, but will also be of benefit to the tribes in informing the development of policies and clinical care that enhances the ability of children to reach their maximum potential.